title: Modulation of virulence gene expression by cell wall active antibiotics in Staphylococcus aureus.
abstract: OBJECTIVE
  To investigate the effect of subinhibitory concentrations of cell wall active antibiotics on virulence gene expression and biofilm formation in Staphylococcus aureus Newman and in laboratory strains.
  
  
  METHODS
  Promoter regions of spa, lukE and agr RNAIII were cloned upstream of a modified luxABCDE reporter. Using disc diffusion assays, the effects of antibiotics were observed on gene expression and quantitative real-time PCR was employed to confirm the results. Assays were performed to measure biofilm formation in wild-type S. aureus and respective spa-deficient and small colony variant mutants in the presence of subinhibitory concentrations of antibiotics.
  
  
  RESULTS
  Expression of spa and lukE was stimulated by subinhibitory concentrations of penicillin and cefalotin, while agr RNAIII expression was not affected. Denser biofilms were formed by S. aureus Newman and its small colony variant in the presence of subinhibitory concentrations of cefalotin.
  
  
  CONCLUSIONS
  Subinhibitory concentrations of certain antibiotics have been shown to stimulate virulence gene expression in S. aureus; this may alter the progression of infection and thus render antimicrobial therapy unreliable. The use of appropriate combinations of antibiotics might be an approach to avoiding this situation. Promoter-lux reporters are sensitive tools for studying the modulation of transcription by antibiotic inhibitors, and could be used to predict novel therapeutic combinations for the treatment of infection.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Subrt
authors.forename: Lili Rosana
authors.initials: LR
authors.lastname: Mesak
authors.forename: Julian
authors.initials: J
authors.lastname: Davies
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000096:biosynthesis; D018441:Biofilms / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects*; D005098:Exotoxins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013205:Staphylococcal Protein A / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D015534:Trans-Activators / Q000096:biosynthesis; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005098:Exotoxins; C115217:LukE protein, Staphylococcus aureus; D013205:Staphylococcal Protein A; D015534:Trans-Activators; D037521:Virulence Factors; D008156:Luciferases